Camizestrant Plus Capivasertib Shows Promise in ER-Positive, HER2-Negative Advanced Breast Cancer

Key Clinical Summary:

• Design/Population: The SERENA-1 trial aimed to evaluate camizestrant plus capivasertib in heavily pretreated, endocrine-resistant patients with ER-positive, HER2-negative advanced breast cancer. 
• Key Outcomes: The combination showed acceptable efficacy and the adverse event profile was consistent with known drug profiles. Diarrhea and nausea were most reported.  
• Clinical Relevance: Combining a selective estrogen receptor degrader with AKT inhibition may offer a new treatment option in endocrine-resistant breast cancer. Further studies are needed to confirm efficacy in larger populations.

According to results from the SERENA-1 trial, camizestrant plus capivasertib shows encouraging efficacy and manageable safety among heavily pretreated, endocrine-resistant patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. 

“Endocrine therapy is designed to reduce ER signaling through direct or indirect mechanisms, and is a key component of the treatment of those with both early and advanced-stage HR-positive breast cancer,” stated Christos Vaklavas, MD, Huntsman Cancer Institute, Salt Lake City, Utah, and coauthors. “Many HR-positive breast cancers are controlled for some time by first-line [endocrine therapy] but subsequently become resistant, highlighting the need for novel [endocrine] and combination therapy approaches to address these mechanisms.” 

In this dose-escalation and dose-expansion study, researchers enrolled 29 pre- or postmenopausal patients who were refractory or intolerant to prior therapies and experienced disease recurrence or progression on at least 1 prior line of endocrine therapy in the advanced or metastatic setting. Patients received 75 mg of once daily camizestrant plus 400 mg of twice daily capivasertib (4 days on; 3 days off) until disease progression or unacceptable toxicity. 

Primary efficacy end points included objective response rate (ORR), duration of response, clinical benefit rate, and progression-free survival (PFS). Safety was assessed through adverse events. 

At a median follow-up of 14.9 months, 6 patients remained on study treatment. The median treatment duration was approximately 8.6 months with camizestrant and approximately 7.3 months with capivasertib. The ORR was 37%, the 24-month clinical benefit rate was 51.7%, and median PFS was 8.3 months. 

Grade ≥3 adverse events were reported in 48.3% of patients and most frequently included diarrhea (10.3%), rash (6.9%), aspartate aminotransferase increase (6.9%), alanine aminotransferase increase (6.9%), and anemia (3.4%). Adverse events led to camizestrant dose reductions in 27.6% of patients and capivasertib dose reductions in 41.4% of patients. Adverse events led to 4 capivasertib treatment discontinuations. No treatment-related deaths were reported. 

“The combination showed encouraging evidence of significant clinical benefit and antitumor activity,” concluded Dr Vaklavas et al. “These results support further investigation of camizestrant 75 mg in combination with capivasertib 400 mg in patients with ER-positive, HER2-negative negative breast cancer.”

Source:

Vaklavas C, Oliveira M, Armstrong AC, et al. Camizestrant in combination with capivasertib for women with ER-positive, HER2-negative advanced breast cancer: results from SERENA-1. ESMO Open. Published online: January 26, 2026. doi:10.1016/j.esmoop.2025.106049